Library Open Repository

Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations

Downloads

Downloads per month over past year

Cohn, AC and Toomes, C and Potter, C and Towns, KV and Hewitt, AW and Inglehearn, CF and Craig, JE and Mackey, DA (2007) Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. American Journal of Ophthalmology, 143 (4). pp. 656-662. ISSN 0002-9394

[img] PDF
4304.pdf | Request a copy
Full text restricted

Abstract

PURPOSE: We identified families with autosomal dominant
optic atrophy (ADOA), determined the number
and type of OPA1 mutations, and investigated the phenotypic
variation and penetrance in ADOA Australian
pedigrees.
DESIGN: Cross-sectional genetics study.

METHODS: Probands were identified on the basis of
characteristic clinical features of ADOA. We screened
the OPA1 gene using single-strand conformational polymorphism,
heteroduplex analysis (SSCP/HA), or by
direct sequencing. Penetrance for pedigrees in which a
mutation of OPA1 had been identified was calculated
initially using all recruited individuals, and subanalysis
was performed using only those families for which there
was total recruitment of siblings.
RESULTS: A total of 406 patients from 17 pedigrees
were recruited, and OPA1 mutations were identified in
11/17 (65%) of these. The mean age at clinical examination
was 38.2 19.9 years (median age, 35 years;
range, four to 83 years). The median best-corrected
visual acuity in OPA1-mutation carriers was 20/70
(range, 20/16 to hand movements [HM]). The penetrance
in Australian ADOA pedigrees in the families
with complete sibling recruitment was 82.5%. On the
other hand, overall penetrance for all individuals harboring
an OPA1 mutation was 88%.
CONCLUSIONS: OPA1 mutations were identified in
11/17 (65%) of the ADOA pedigrees in this study. The
penetrance in our cohort was lower than originally
described (82.5% vs 98%) but higher than some recent
studies since the availability of genotyping. It is anticipated
that this figure would be even lower as more
asymptomatic individuals are identified. There are likely
to be other genetic and environmental modifiers influencing
disease penetrance.

Item Type: Article
Journal or Publication Title: American Journal of Ophthalmology
Publisher: ELSEVIER SCIENCE INC,
Page Range: pp. 656-662
ISSN: 0002-9394
Identification Number - DOI: 10.1016/j.ajo.2006.12.038
Additional Information:

The definitive version is available at http://www.sciencedirect.com

Date Deposited: 07 Apr 2008 14:32
Last Modified: 18 Nov 2014 03:35
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page